[Subarachnoid hemorrhage in a young girl]. / Een meisje met een subarachnoïdale bloeding.

BACKGROUND: Subarachnoid hemorrhage in children is rare. The most common cause is trauma, followed by an arteriovenous malformation, aneurysm or tumor. CASE DESCRIPTION: We describe the case of an 11-year-old girl who developed sudden headache with nausea and vomiting during athletics training. Her neurological exam was normal. With imaging and a lumbar puncture a subarachnoid hemorrhage was diagnosed, based on a ruptured saccular aneurysm of the right middle cerebral artery. Endovascular treatment was unsuccessful, after which the aneurysm was treated surgically. Postoperative recovery was uneventful. Additional tests for underlying conditions were negative. CONCLUSION: Also in a child with acute headache, nausea, and vomiting, the diagnosis of a subarachnoid hemorrhage should be considered, even if neurological examination is normal. Expeditious diagnosis and treatment are important in order to prevent rebleeding.

Validity of the modified Rankin Scale in patients with aneurysmal subarachnoid hemorrhage: a randomized study.

PURPOSE: The modified Rankin Scale (mRS), a clinician-reported outcome measure of global disability, has never been validated in patients with aneurysmal subarachnoid hemorrhage (aSAH). The aims of this study are to assess: (1) convergent validity of the mRS; (2) responsiveness of the mRS; and (3) the distribution of mRS scores across patient-reported outcome measures (PROMs). METHODS: This is a prospective randomized multicenter study. The mRS was scored by a physician for all patients, and subsequently by structured interview for half of the patients and by self-assessment for the other half. All patients completed EuroQoL 5D-5L, RAND-36, Stroke Specific Quality of Life scale (SS-QoL) and Global Perceived Effect (GPE) questionnaires. Convergent validity and responsiveness were assessed by testing hypotheses. RESULTS: In total, 149 patients with aSAH were included for analysis. The correlation of the mRS with EQ-5D-5L was r = - 0.546, while with RAND-36 physical and mental component scores the correlation was r = - 0.439and r = - 0.574 respectively, and with SS-QoL it was r = - 0.671. Three out of four hypotheses for convergent validity were met. The mRS assessed through structured interviews was more highly correlated with the mental component score than with the physical component score of RAND-36. Improvement in terms of GPE was indicated by 83% of patients; the mean change score of these patients on the mRS was - 0.08 (SD 0.915). None of the hypotheses for responsiveness were met. CONCLUSION: The results show that the mRS generally correlates with other instruments, as expected, but it lacks responsiveness. A structured interview of the mRS is best for detecting disabling neuropsychological complaints. REGISTRATION: URL: https://trialsearch.who.int ; Unique identifier: NL7859, Date of first administration: 08-07-2019.

Association between Dural AVFs and Cerebral Venous Thrombosis.

BACKGROUND AND PURPOSE: Recent reports suggest an association between dural AVFs and cerebral venous thrombosis. We aimed to investigate the specific temporal and anatomic association between the 2 conditions. MATERIALS AND METHODS: A consecutive cohort of adult patients with dural AVFs was seen at Amsterdam University Medical Centers (2007-2020). An experienced neuroradiologist re-evaluated the presence and imaging characteristics of dural AVFs and cerebral venous thrombosis on all available imaging. The temporal (previous/concurrent/subsequent) and anatomic (same/adjacent/unrelated venous sinus or vein) association between dural AVFs and cerebral venous thrombosis was determined. RESULTS: Among 178 patients with dural AVFs, the mean age was 58.3 (SD, 13.2) years and 85 (48%) were women. Of 55 patients (31%) with cerebral venous thrombosis, 34 (62%) were women. Four patients (7%) had cerebral venous thrombosis before the development of a dural AVF, 33 (60%) had cerebral venous thrombosis at the time of dural AVF diagnosis (concurrent), and 18 (33%) developed cerebral venous thrombosis during follow-up after conservative treatment. The incidence rate of cerebral venous thrombosis after a dural AVF was 79 per 1000 person-years (95% CI, 50-124). In 45 (82%) patients with dural AVFs and cerebral venous thrombosis, the thrombosis was located in the same venous sinus as the dural AVF, whereas in 8 (15%) patients, thrombosis occurred in a venous sinus adjacent to the dural AVF. CONCLUSIONS: One-third of patients with a dural AVF in this study were diagnosed with cerebral venous thrombosis. In almost two-thirds of patients, cerebral venous thrombosis was diagnosed prior to or concurrent with the dural AVF. In 97% of patients, there was an anatomic association between the dural AVF and cerebral venous thrombosis. These data support the hypothesis of a bidirectional association between the 2 diseases.

Inter-method reliability of the modified Rankin Scale in patients with subarachnoid hemorrhage.

BACKGROUND AND OBJECTIVES: The modified Rankin Scale (mRS) is one of the most frequently used outcome measures in trials in patients with an aneurysmal subarachnoid hemorrhage (aSAH). The assessment method of the mRS is often not clearly described in trials, while the method used might influence the mRS score. The aim of this study is to evaluate the inter-method reliability of different assessment methods of the mRS. METHODS: This is a prospective, randomized, multicenter study with follow-up at 6 weeks and 6 months. Patients aged ≥ 18 years with aSAH were randomized to either a structured interview or a self-assessment of the mRS. Patients were seen by a physician who assigned an mRS score, followed by either the structured interview or the self-assessment. Inter-method reliability was assessed with the quadratic weighted kappa score and percentage of agreement. Assessment of feasibility of the self-assessment was done by a feasibility questionnaire. RESULTS: The quadratic weighted kappa was 0.60 between the assessment of the physician and structured interview and 0.56 between assessment of the physician and self-assessment. Percentage agreement was, respectively, 50.8 and 19.6%. The assessment of the mRS through a structured interview and by self-assessment resulted in systematically higher mRS scores than the mRS scored by the physician. Self-assessment of the mRS was proven feasible. DISCUSSION: The mRS scores obtained with different assessment methods differ significantly. The agreement between the scores is low, although the reliability between the assessment methods is good. This should be considered when using the mRS in clinical trials. TRIAL REGISTRATION: www.trialregister.nl ; Unique identifier: NL7859.

Prediction of Outcome Using Quantified Blood Volume in Aneurysmal SAH.

BACKGROUND AND PURPOSE: In patients with SAH, the amount of blood is strongly associated with clinical outcome. However, it is commonly estimated with a coarse grading scale, potentially limiting its predictive value. Therefore, we aimed to develop and externally validate prediction models for clinical outcome, including quantified blood volumes, as candidate predictors. MATERIALS AND METHODS: Clinical and radiologic candidate predictors were included in a logistic regression model. Unfavorable outcome was defined as a modified Rankin Scale score of 4-6. An automatic hemorrhage-quantification algorithm calculated the total blood volume. Blood was manually classified as cisternal, intraventricular, or intraparenchymal. The model was selected with bootstrapped backward selection and validated with the R 2, C-statistic, and calibration plots. If total blood volume remained in the final model, its performance was compared with models including location-specific blood volumes or the modified Fisher scale. RESULTS: The total blood volume, neurologic condition, age, aneurysm size, and history of cardiovascular disease remained in the final models after selection. The externally validated predictive accuracy and discriminative power were high (R 2 = 56% ± 1.8%; mean C-statistic = 0.89 ± 0.01). The location-specific volume models showed a similar performance (R 2 = 56% ± 1%, P = .8; mean C-statistic = 0.89 ± 0.00, P = .4). The modified Fisher models were significantly less accurate (R 2 = 45% ± 3%, P < .001; mean C-statistic = 0.85 ± 0.01, P = .03). CONCLUSIONS: The total blood volume-based prediction model for clinical outcome in patients with SAH showed a high predictive accuracy, higher than a prediction model including the commonly used modified Fisher scale.

Platelet transfusion in patients with aneurysmal subarachnoid hemorrhage is associated with poor clinical outcome.

Patients with subarachnoid hemorrhage (SAH) who are using antiplatelet drugs prior to their hemorrhage, often receive platelet transfusions to reverse antiplatelet effects prior to life-saving surgical interventions. However, little is known about the effect of platelet transfusion on patient outcome in these patients. The aim of this study is to investigate the effect of platelet transfusion on clinical outcome in patients with aneurysmal SAH (aSAH) who use antiplatelet agents. Consecutive adult patients with an aSAH admitted between 2011 and 2015 to the Academic Medical Center (Amsterdam, the Netherlands) were included. Demographic characteristics and in-hospital complications were compared and clinical outcome was assessed after six months. Multivariable logistic regression analysis was performed to correct for confounding variables. A total of 364 patients with an aSAH were included. Thirty-eight (10%) patients underwent platelet transfusion during admission. Patients receiving platelet transfusion had worse clinical outcome (modified Rankin Scale score 4-6) at six months compared to patients without platelet transfusion (65% versus 32%, odds ratio 4.0, 95% confidence interval:1.9-8.1). Multivariable logistic regression analysis showed that platelet transfusion during admission was associated with unfavorable clinical outcome after six months; adjusted for age, treatment modality, modified Fisher and WFNS on admission (adjusted odds ratio 3.3, 95% confidence interval: 1.3-8.4). In this observational study, platelet transfusion was associated with poor clinical outcome at six months after correcting for confounding influences. In aSAH patients who need surgical treatment at low risk of bleeding, the indication for platelet transfusion needs careful weighing of the risk-benefit-balance.

Short-term tranexamic acid treatment reduces in-hospital mortality in aneurysmal sub-arachnoid hemorrhage: A multicenter comparison study.

BACKGROUND: Recurrent bleeding is one of the major causes of morbidity and mortality in patients with aneurysmal subarachnoid hemorrhage (aSAH). Antifibrinolytic therapy is known to reduce recurrent bleeding, however, its beneficial effect on outcome remains unclear. The effect of treatment with tranexamic acid (TXA) until aneurysm treatment on clinical outcome is evaluated. METHODS: Patients with an aSAH from two high-volume tertiary referral treatment centers in the Netherlands, Academic Medical Center (AMC) and Radboud University Medical Center (RUMC), between January 2012 and December 2015 were included. Patients were classified into one of two groups; standard treatment or TXA treatment. Demographic and clinical characteristics, in-hospital complications and clinical outcome were compared between the two groups. Multivariate logistic regression was used to adjust for the influence of treatment center and baseline differences. RESULTS: Standard treatment was given in 509 patients, and 119 patients received additional TXA therapy before aneurysm occlusion. Patients treated with TXA did not experience less recurrent bleeding adjusted or unadjusted for treatment center (adjusted odds ratio [aOR] 0.80, 95% confidence interval [95% CI]: 0.37-1.73). In-hospital mortality, was significantly lower in the TXA group than the standard care group (adjusted OR [aOR] 0.42, 95% CI: 0.20-0.85). Poor outcome (mRS 4-6) assessed after six months was not different between treatment groups (aOR 1.05, 95% CI: 0.64-1.74). CONCLUSIONS: Pooled data from two high-volume treatment centers did not show improved clinical outcome after additional TXA treatment in aSAH patients. However, TXA treatment was associated with a decrease in mortality.

Association of Quantified Location-Specific Blood Volumes with Delayed Cerebral Ischemia after Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND AND PURPOSE: Delayed cerebral ischemia is a severe complication of aneurysmal SAH and is associated with a high case morbidity and fatality. The total blood volume and the presence of intraventricular blood on CT after aneurysmal SAH are associated with delayed cerebral ischemia. Whether quantified location-specific (cisternal, intraventricular, parenchymal, and subdural) blood volumes are associated with delayed cerebral ischemia has been infrequently researched. This study aimed to associate quantified location-specific blood volumes with delayed cerebral ischemia. MATERIALS AND METHODS: Clinical and radiologic data were collected retrospectively from consecutive patients with aneurysmal SAH with available CT scans within 24 hours after ictus admitted to 2 academic centers between January 2009 and December 2011. Total blood volume was quantified using an automatic hemorrhage-segmentation algorithm. Segmented blood was manually classified as cisternal, intraventricular, intraparenchymal, or subdural. Adjusted ORs with 95% confidence intervals for delayed cerebral ischemia per milliliter of location-specific blood were calculated using multivariable logistic regression analysis. RESULTS: We included 282 patients. Per milliliter increase in blood volume, the adjusted OR for delayed cerebral ischemia was 1.02 (95% CI, 1.01-1.04) for cisternal, 1.02 (95% CI, 1.00-1.04) for intraventricular, 0.99 (95% CI, 0.97-1.02) for intraparenchymal, and 0.96 (95% CI, 0.86-1.07) for subdural blood. CONCLUSIONS: Our findings suggest that in patients with aneurysmal subarachnoid hemorrhage, the cisternal blood volume has a stronger relation with delayed cerebral ischemia than the blood volumes at other locations in the brain.

Ruptured middle cerebral artery aneurysms with a concomitant intraparenchymal hematoma: the role of hematoma volume.

PURPOSE: To study whether clinical outcome data from our patient cohort could give support to the new recommendation in the AHA/ASA guidelines for the management of aneurysmal subarachnoid hemorrhage that states "that microsurgical clipping may receive increased consideration in patients with ruptured middle cerebral artery (MCA) aneurysms and large (>50 mL) intraparenchymal hematomas", while clinical outcome data supporting this recommendation are sparse. METHODS: We reviewed the clinical and radiological data of 81 consecutive patients with MCA aneurysms and concomitant hematomas admitted between January 2006 and December 2015. The relation between (semi-automatically quantified) hematoma volume (< or > 50 ml), neurological condition on admission (poor: GCS < 8 or non-reactive pupils), treatment strategies (no treatment, coiling, or clipping with or without decompression and/or clot removal), and outcome (favorable: mRS score 0-3) was evaluated. RESULTS: Clinical outcome data were available for 76 patients. A significant difference in favorable outcome (17 vs 68%) was seen when comparing patients with poor and good neurological condition on admission (p < 0.01). Patients with hematomas > 50 ml had similar outcomes for coiling and clipping, all underwent decompression. Patients with hematomas < 50 ml did not show differences in favorable outcome when comparing coiling and clipping with (33 and 31%) or without decompression (90 and 88%). CONCLUSION: Poor neurological condition on admission, and not large intraparenchymal hematoma volume, was associated with poor clinical outcome. Therefore, even in patients with large hematomas, the neurological condition on admission and the aneurysm configuration seem to be equally important factors to determine the most appropriate treatment strategy.

A strategy to expeditious invasive treatment improves clinical outcome in comatose patients with aneurysmal subarachnoid haemorrhage.

BACKGROUND: In patients with poor clinical condition after aneurysmal subarachnoid haemorrhage (aSAH), treatment is often deferred until patients show signs of improvement. Early external ventricular drainage and aneurysm occlusion may improve prognosis also in poor grade patients. The clinical outcome of an expeditious approach was compared with that of a conservative approach. METHODS: In all, 285 consecutive World Federation of Neurological Surgeons (WFNS) grade V aSAH patients admitted to three university hospitals between January 2000 and June 2007 were included. Two hospitals followed an expeditious approach, one a more conservative approach. Groups were compared with respect to demographic and clinical characteristics and outcome. Univariable and multivariable analyses were performed to determine the associations with good outcome (Glasgow Outcome Scale scores 4-5), using logistic regression models. RESULTS: Good outcome was seen more often in expeditiously treated patients [22% vs. 11%; odds ratio (OR) 2.24, 95% confidence interval (CI) 1.17-4.27]. Expeditiously treated patients more often underwent aneurysm occlusion than conservatively treated patients (64% vs. 27%; OR 4.86, 95% CI 2.93-8.05) and placement of an external ventricular catheter (82% vs. 31%; OR 10.05, CI 5.72-10.66). There was no significant difference in rebleeding between patient groups. Occlusion of the aneurysm was the only variable that remained significant in the multivariable model with an OR of 43.73 (95% CI 10.34-184.97). CONCLUSIONS: An expeditious invasive treatment strategy in WFNS grade V aSAH patients can lead to a better outcome. Hesitance in the early stages seems a self-fulfilling prophecy for a poor outcome.

Clinical and Laboratory Characteristics for the Diagnosis of Bacterial Ventriculitis After Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: The diagnosis of nosocomial bacterial ventriculitis in patients with subarachnoid hemorrhage (SAH) can be challenging. METHODS: We performed a retrospective study on the diagnostic accuracy of clinical and laboratory characteristics for the diagnosis of bacterial ventriculitis in 209 consecutive patients with an aneurysmal SAH admitted in a tertiary referral center from 2008 to 2010. Diagnostic value of clinical characteristics and inflammatory indexes in CSF and blood were determined for three diagnostic categories: (1) no suspicion for bacterial ventriculitis; (2) clinical suspicion for bacterial ventriculitis, defined as initiation of empirical antibiotic treatment for ventriculitis, but negative CSF cultures; and (3) CSF culture-positive bacterial ventriculitis. RESULTS: Empirical antibiotics for suspected ventriculitis was initiated in 48 of 209 (23 %) patients. CSF cultures were positive in 11 (5 %) patients. Within the group of suspected ventriculitis, only longer duration of CSF drainage and lower CSF red blood cell counts predicted for culture positivity. None of the other clinical features or inflammatory indexes in CSF and blood were associated with culture-proven bacterial ventriculitis. CONCLUSIONS: Nosocomial bacterial ventriculitis in patients with aneurysmal SAH is often suspected but confirmed by culture in a minority of cases. Improvement of diagnostics for nosocomial bacterial ventriculitis in patients with aneurysmal SAH is needed.

Association of Automatically Quantified Total Blood Volume after Aneurysmal Subarachnoid Hemorrhage with Delayed Cerebral Ischemia.

BACKGROUND AND PURPOSE: The total amount of extravasated blood after aneurysmal subarachnoid hemorrhage, assessed with semiquantitative methods such as the modified Fisher and Hijdra scales, is known to be a predictor of delayed cerebral ischemia. However, prediction rates of delayed cerebral ischemia are moderate, which may be caused by the rough and observer-dependent blood volume estimation used in the prediction models. We therefore assessed the association between automatically quantified total blood volume on NCCT and delayed cerebral ischemia. MATERIALS AND METHODS: We retrospectively studied clinical and radiologic data of consecutive patients with aneurysmal SAH admitted to 2 academic hospitals between January 2009 and December 2011. Adjusted ORs with associated 95% confidence intervals were calculated for the association between automatically quantified total blood volume on NCCT and delayed cerebral ischemia (clinical, radiologic, and both). The calculations were also performed for the presence of an intraparenchymal hematoma and/or an intraventricular hematoma and clinical delayed cerebral ischemia. RESULTS: We included 333 patients. The adjusted OR of total blood volume for delayed cerebral ischemia (clinical, radiologic, and both) was 1.02 (95% CI, 1.01-1.03) per milliliter of blood. The adjusted OR for the presence of an intraparenchymal hematoma for clinical delayed cerebral ischemia was 0.47 (95% CI, 0.24-0.95) and of the presence of an intraventricular hematoma, 2.66 (95% CI, 1.37-5.17). CONCLUSIONS: A higher total blood volume measured with our automated quantification method is significantly associated with delayed cerebral ischemia. The results of this study encourage the use of rater-independent quantification methods in future multicenter studies on delayed cerebral ischemia prevention and prediction.

Time intervals from subarachnoid hemorrhage to rebleed.

The most threatening early complication and predictor of poor outcome after an aneurysmal subarachnoid hemorrhage (aSAH) is a rebleed. To evaluate what proportion of rebleeds might be prevented by early treatment, we assessed the time interval from the initial hemorrhage to rebleed, and the location of the patient at the time of rebleed. Patient characteristics, World Federation of Neurological Surgeons grade on admission and modified Rankin Scale outcome scores, referring hospitals and time intervals from initial hemorrhage to treatment of 293 patients treated between 2008 and 2011 were evaluated. Time intervals to rebleeds and location of the patients at the time of rebleed were retrieved. Rebleeds were confirmed by CT in 12% of patients, and an additional 4% of patients was diagnosed as having a possible rebleed. Sixty percent of rebleeds occurred after admission to the treatment center. Almost all rebleeds occurred within 24 h, with a median time interval between initial hemorrhage and rebleed of 180 min. A significantly shorter time to treatment and a higher mortality were seen in the group of patients with a rebleed. Approximately, one in six patients with an aSAH had a rebleed, of which a majority might have been preventable because they occurred after admission to the treatment center. A reduction in the rebleed rate seems feasible by securing the aneurysm as soon as possible by improving in-hospital logistics for early aneurysm treatment. Alternative options, such as immediate administration of antifibrinolytics, are being explored in a multicenter trial.

Beta-cell dysfunction and insulin resistance after subarachnoid haemorrhage.

BACKGROUND: Hyperglycaemia is a common finding and an independent risk factor for increased morbidity and mortality in aneurysmal subarachnoid haemorrhage (SAH). Although in these patients hyperglycaemia is commonly ascribed to insulin resistance, there is little understanding of underlying mechanisms. AIMS: To prospectively study temporal disturbances of glucose metabolism after aneurysmal SAH in patients without known abnormalities of glucose metabolism and to explore possible correlations with markers of stress. METHODS: In consecutive aneurysmal SAH patients not subjected to insulin therapy, in-hospital and follow-up oral glucose tolerance tests (OGTTs) and assessments of insulin resistance, pancreatic ß-cell function, free fatty acids (FFA) and cortisol were performed and compared with reference values. RESULTS: We included 13 patients. In the first 2 weeks of admission, median fasting glucose and FFA levels were elevated while insulin levels were not. OGTTs were indicative of glucose intolerance in all patients at days 3 and 7, while on follow-up 1 patient had glucose intolerance and all patients had normal fasting glucose levels. Pancreatic ß-cell function was impaired throughout the first week and insulin resistance from day 4 to 10. Levels of cortisol correlated with higher fasting glucose and increased FFA. FFA in turn correlated with pancreatic ß-cell dysfunction. CONCLUSIONS: Aneurysmal SAH patients have transient abnormalities of glucose metabolism. During the first week, it appears to result predominantly from transient pancreatic ß-cell dysfunction, in combination with insulin resistance.

Exogenous spermine reduces ischemic damage in a model of focal cerebral ischemia in the rat.

Alterations in polyamine metabolism during and after global or focal cerebral ischemia can produce a multiplicity of effects on brain such as modification in mitochondria calcium buffering capacity, exacerbating glutamate-mediated neurotoxicity, and impairment of the blood-brain barrier. In this study, the endogenous polyamine spermine was administered intravenously 30 min prior to temporary focal cerebral ischemia in rats induced by clipping of the left middle cerebral and bilateral common carotid arteries for 3 h. Three days after removal of the microclips, intracardiac perfusion with 2% 2,3,5-triphenyl tetrazolium chloride was performed. Coronal slices were cut, photographed, and examined for cortical infarct volume. Spermine reduced infarct volume in a dose-dependent fashion. This study demonstrates that the use of polyamines may be considered as a powerful tool in prevention of ischemic tissue damage following focal cerebral ischemia.

A comparative study of the effects of two nitric oxide synthase inhibitors and two nitric oxide donors on temporary focal cerebral ischemia in the Wistar rat.

OBJECT: A critical review of the literature indicates that the effects of nitric oxide synthase (NOS) inhibitors on focal cerebral ischemia are contradictory. In this experiment the authors methodically examined the dose-dependent effects of two NOS inhibitors and two NO donors on cortical infarction volume in an animal model of temporary focal cerebral ischemia simulating potential ischemia during neurovascular interventions. METHODS: Ninety-two Wistar rats underwent 3 hours of combined left middle cerebral artery and bilateral common carotid artery occlusion after having been anesthetized with 1% halothane. A nonselective NOS inhibitor, N(G)-nitro-L-arginine-methyl-ester (L-NAME), and two NO donors, 3-morpholinosydnonimine hydrochloride and NOC-18, DETA/NO, (Z)-1-[2(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-i um-1,2-diolate, were administered intravenously 30 minutes before ischemia was induced. A selective neuronal NOS inhibitor, 7-nitroindazole (7-NI), was administered intraperitoneally in dimethyl sulfoxide (DMSO) 60 minutes before ischemia was induced. Two ischemic control groups, to which either saline or DMSO was administered, were also included in this study. Seventy-two hours after flow restoration, the animals were perfused with tetrazolium chloride for histological evaluation. Cortical infarction volume was significantly reduced by 71% in the group treated with 1 mg/kg L-NAME when compared with the saline-treated ischemic control group (27.1+/-37 mm3 compared with 92.5+/-26 mm3, p < 0.05). The NOS inhibitor 7-NI significantly reduced cortical infarction volume by 70% and by 92% at doses of 10 and 100 mg/kg: 35.2+/-32 mm3 (p < 0.05) and 9+/-13 mm3 (p < 0.005), respectively, when compared with the DMSO-treated ischemic control group (119+/-43 mm3). There was no significant difference between the saline-treated and DMSO-treated ischemic control groups. Treatment with NO donors did not significantly alter cortical infarction volume. CONCLUSIONS: These results support an important role for NO in ischemic neurotoxicity and indicate that neuronal NOS inhibition may be valuable in reducing cortical injury in patients suffering temporary focal cerebral ischemia during neurovascular procedures.

Reproducibility of cerebral cortical infarction in the wistar rat after middle cerebral artery occlusion.

Although middle cerebral artery (MCA) occlusion in the rat is often used to study focal cerebral ischemia, the model of ischemia affects the size and reproducibility of infarction. The purpose of this experiment was to methodically examine different preparations to determine the optimum focal cerebral ischemia model to produce a reproducible severe ischemic injury. Eighty-two Wistar rats underwent either 1 hour, 3 hour, or permanent MCA occlusion combined with no, unilateral, or bilateral common carotid artery artery (CCA) occlusion. Three days after ischemia, the animals were prepared for tetrazolium chloride assessment of infarction size. One-hour MCA occlusion produced a coefficient of variation (CV) of 200% with an infarction volume of 20.3+/-10.5 mm(3). Adding unilateral or bilateral CCA occlusion resulted in a CV of 134% and 101%, respectively. Three-hour MCA occlusion combined with bilateral CCA occlusion decreased the CV to 58% with a cortical infarction volume of 82.6+/-12.1 mm(3), P<05, compared with 1-hour MCA occlusion with or without CCA occlusion. Permanent MCA occlusion combined with 3 hours of bilateral CCA occlusion resulted in a CV of 47% with a cortical infarction volume of 89.6+/-16.0 mm(3). These results indicate that 3-hour MCA occlusion combined with bilateral CCA occlusion provide consistently a large infarction volume after temporary focal cerebral ischemia.